Breath sampling mask and system

ABSTRACT

Embodiments herein include a breath sampling mask, systems, and related methods. In an embodiment, a breath sensing system is included. The breath sensing system can include a breath sampling mask. The breath sampling mask can include a mask housing configured to cover a portion of the face of a patient. The mask housing can define a breath receiving chamber. The breath sampling mask can include a chemical sensor element in fluid communication with the breath sampling mask, where the chemical sensor element can include a plurality of discrete binding detectors. The chemical sensor element can interface with a breath sample collected through the breath sampling mask. Other embodiments are also included herein.

This application is a Continuation of U.S. application Ser. No.16/280,644, filed on Feb. 20, 2019, which claims the benefit of U.S.Provisional Application No. 62/632,552, filed Feb. 20, 2018, thecontents of which are herein incorporated by reference in theirentirety.

FIELD OF THE TECHNOLOGY

The present application relates to a breath sampling mask and systemsand methods related to the same.

BACKGROUND

The accurate detection of diseases can allow clinicians to provideappropriate therapeutic interventions. The early detection of diseasescan lead to better treatment outcomes. Diseases can be detected usingmany different techniques including analyzing tissue samples, analyzingvarious bodily fluids, diagnostic scans, genetic sequencing, and thelike.

Some disease states result in the production of specific chemicalcompounds. In some cases, volatile organic compounds (VOCs) releasedinto a gaseous sample of a patient can be hallmarks of certain diseases.The detection of these compounds or differential sensing of the same canallow for the early detection of particular disease states.

The breath of a patient provides an ideal gas for diagnostic samplingpurposes. As a part of tidal respiration, air is drawn in through thenose and/or mouth and into the lungs. By its presence in close contactwith moist internal tissues, the inspired air is warmed, humidified, andpicks up volatile organic compounds. This air is then expired outthrough the nose and/or mouth.

SUMMARY

In a first aspect, a breath sensing system is included. The breathsampling system can include a breath sampling mask. The breath samplingmask can include a mask housing configured to cover a portion of theface of a patient, the mask housing defining a breath receiving chamber.The breath sampling system can also include a chemical sensor element influid communication with the breath sampling mask. The chemical sensorelement can include a plurality of discrete binding detectors. Thechemical sensor element can be configured to interface with a breathsample collected through the breath sampling mask.

In a second aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include circuitry for generating signals from thediscrete binding detectors.

In a third aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a breath sampling mask including a nose clipfor helping to secure the breath sampling mask to the face of a patient.

In a fourth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a sensor such as one or more of a temperaturesensor, a heart rate sensor, and a blood pressure sensor.

In a fifth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a sensor such as one or more of an ambienttemperature sensor, an ambient humidity sensor, an internal temperaturesensor, and an internal humidity sensor.

In a sixth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a removable breath sample container disposedwithin the mouth chamber.

In a seventh aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a gas outflow conduit in fluid communicationwith the breath receiving chamber.

In an eighth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a chemical sensor holder configured to allowremovable mounting of a chemical sensor element.

In a ninth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the chemicalsensor holder can be disposed within the breath receiving chamber.

In a tenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a chemical sensor holder housing in fluidcommunication with the breath receiving chamber, wherein the chemicalsensor element can be disposed within the chemical sensor holderhousing.

In an eleventh aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsensing system can include a filter in fluid communication with theone-way airflow valve.

In a twelfth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, a breathsampling mask is included. The breath sampling mask can include a maskhousing configured to cover a portion of the face of a patient. The maskhousing can define a chamber. The mask configured to remove volatileorganic compounds from air drawn in through the mask housing.

In a thirteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsampling mask can include a sensor such as one or more of a temperaturesensor, a heart rate sensor, and a blood pressure sensor.

In a fourteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsampling mask can include a nose clip member for helping to secure thebreath sampling mask to the patient.

In a fifteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, a sensor canbe attached to a nose clip member.

In a sixteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the maskhousing of the breath sampling mask can include a dividing wallisolating the chamber into a nasal chamber and a mouth chamber.

In a seventeenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsampling mask can include a one-way airflow valve in fluid communicationwith the nasal chamber and an area outside of the mask housing, wherethe one-way airflow valve only allows a flow of air from the areaoutside of the mask housing into the nasal chamber.

In an eighteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsampling mask can include a chemical sensor holder configured to allowremovable mounting of a chemical sensor element. The chemical sensorholder can be disposed within the mouth chamber of the breath samplingmask.

In a nineteenth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, the breathsampling mask can include a sensor such as one or more of an ambienttemperature sensor, an ambient humidity sensor, an internal temperaturesensor, and an internal humidity sensor.

In a twentieth aspect, in addition to one or more of the preceding orfollowing aspects, or in the alternative to some aspects, a method ofdetermining the presence of one or more disease states of a patient isincluded. The method can include putting a breath sampling mask on apatient; alerting the patient to breathe in and out to generate a breathsample; contacting the breath sample with a chemical sensor element, thechemical sensor element including a plurality of discrete bindingdetectors; using a measurement circuit to generate signals from thediscrete binding detectors; and evaluating the signals by comparing themto previously obtained sets of signals or signal patterns.

This summary is an overview of some of the teachings of the presentapplication and is not intended to be an exclusive or exhaustivetreatment of the present subject matter. Further details are found inthe detailed description and appended claims. Other aspects will beapparent to persons skilled in the art upon reading and understandingthe following detailed description and viewing the drawings that form apart thereof, each of which is not to be taken in a limiting sense. Thescope of the present application is defined by the appended claims andtheir legal equivalents.

BRIEF DESCRIPTION OF THE FIGURES

The technology may be more completely understood in connection with thefollowing drawings, in which:

FIG. 1 is a schematic view of a patient showing portions of respiratorypathways.

FIG. 2 is a schematic view of a breath sampling mask as worn by apatient in accordance with various embodiments herein.

FIG. 3 is a schematic view of a breath sampling mask as worn by apatient in accordance with various embodiments herein.

FIG. 4 is a schematic cutaway view of a breath sampling mask as worn bya patient in accordance with various embodiments herein.

FIG. 5 is a schematic cutaway view of a breath sampling mask as worn bya patient in accordance with various embodiments herein.

FIG. 6 is a schematic cutaway view of a breath sampling mask as worn bya patient in accordance with various embodiments herein.

FIG. 7 is a schematic view of a breath sampling system in accordancewith various embodiments herein.

FIG. 8 is a schematic view of a breath sampling system in accordancewith various embodiments herein.

FIG. 9 is a schematic view of a breath sampling system in accordancewith various embodiments herein.

FIG. 10 is a schematic view of a breath sampling system in accordancewith various embodiments herein.

FIG. 11 is a schematic view of a breath sampling system in accordancewith various embodiments herein.

FIG. 12 is a schematic view of a breath sampling mask in accordance withvarious embodiments herein.

FIG. 13 is a schematic view of a breath sampling mask in accordance withvarious embodiments herein.

FIG. 14 is a schematic view of a breath sampling mask in accordance withvarious embodiments herein.

FIG. 15 is a schematic cutaway view of a breath sampling mask inaccordance with various embodiments herein.

FIG. 16 is a schematic isometric view of a breath sampling mask inaccordance with various embodiments herein.

FIG. 17 a schematic bottom plan view of a breath sampling mask inaccordance with various embodiments herein.

FIG. 18 a schematic top plan view of a chemical sensor element inaccordance with various embodiments herein.

FIG. 19 is a schematic diagram of a portion of a measurement zone inaccordance with various embodiments herein.

FIG. 20 is a schematic perspective view of a graphene varactor inaccordance with various embodiments herein.

FIG. 21 is a schematic cross-sectional view of a portion of a graphenevaractor in accordance with various embodiments herein.

FIG. 22 is a circuit diagram of a passive sensor circuit and a portionof a reading circuit is shown in accordance with various embodimentsherein.

While the technology is susceptible to various modifications andalternative forms, specifics thereof have been shown by way of exampleand drawings, and will be described in detail. It should be understood,however, that the application is not limited to the particularembodiments described. On the contrary, the application is to covermodifications, equivalents, and alternatives falling within the spiritand scope of the technology.

DETAILED DESCRIPTION

The breath of a patient provides an ideal gas for diagnostic samplingpurposes. As a part of tidal respiration, air is drawn in through thenose and/or mouth and into the lungs. By its presence in close contactwith moist internal tissues, the inspired air is warmed, humidified, andpicks up volatile organic compounds (VOCs). This air is then expired outthrough the nose and/or mouth.

In some instances, the VOCs present in exhaled breath can be hallmarksof certain diseases, including but not limited to cancers, includinglung cancer, blood-borne cancers, prostate cancer, rectal cancer, breastcancer, liver cancer, pancreatic cancer, or to other disorders such aschronic obstructive pulmonary disease, diabetes, heart failure, and thelike. Detection of VOCs in the breath of a patient directly from thegaseous form can provide an accurate mechanism for determining one ormore diseased states.

Referring now to FIG. 1, a schematic view is shown of a patient 100showing portions of respiratory pathways. Air can be inspired throughthe nose 108 and into nasal passages 104 or through the mouth 110 andinto oral passages 106 eventually reaching the lungs 102. The inspiredair is warmed, humidified, and picks up volatile organic compoundsduring its passage to the lungs, while it remains in the lungs, andfurther during expiration on its way back out of the lungs. The air isthen expired through the nasal passages 104 and out the nose 108 and/orthrough oral passages 106 and out the mouth 110.

In accordance with various embodiments herein, a breath sampling mask isincluded which can aid in one or more of: capturing breath samples,controlling how the breath samples are generated and treated, andproviding additional data regarding the patient and/or their currentphysiological state. FIG. 2 is a schematic view of a breath samplingmask 200 as worn by a patient 100 in accordance with various embodimentsherein. The breath sampling mask 200 can include one or more elasticmembers 202, 204 configured to secure the breath sampling mask 200 tothe patient's face. The pressure of the breath sampling mask 200 on theface can aid in forming an air tight connection of the breath samplingmask 200 to the patient's face.

In the embodiment of FIG. 2, when the patient creates a negativepressure inside the breath sampling mask 200, air can be drawn from theambient environment into the breath sampling mask 200 through theexterior surface of breath sampling mask 200 (or a portion thereof), asindicated in FIG. 2 by air inflow arrows 210, 212, 214, and 216. Assuch, the breath sampling mask 200, or portions thereof, can be made ofa porous material (one or more layers of material) to allow air to bedrawn in, in this way. Porous materials can include, but are not limitedto, woven and non-woven fibrous materials, porous cellulosic materials,porous polymers, porous or non-porous materials assuming porousstructures such as grids, weaves, sieves, and the like. However, inother embodiments, the breath sampling mask 200, or portions thereof,can be made of a non-porous material. Non-porous materials can include,but are not limited to, polymers, metals, cellulosic materials,composites, metals, ceramics, and the like.

In some embodiments, breath sampling mask 200 can include filters orconditioned surfaces to treat the incoming air such that it can do oneor more of: filtering particulate matter from the air, providinghumidity control, providing a filter for organic or inorganic matter,and providing for adsorption of compounds and/or particulates in theambient environment. By way of example, a carbon surface can be includedon the exterior to filter out environmental particulates and/orenvironmental volatile organic compounds (VOCs). For example, a carbonmaterial can be sprayed on, or otherwise applied to, an outer surface ofthe breath sampling mask 200. In some embodiments, the breath samplingmask 200 can include a carbon layer disposed within the mask itself. Forexample, a carbon material can be integrated into a material layer usedto make the breath sampling mask 200 and/or sandwiched in between layersof material used to make the breath sampling mask 200. Carbon herein canbe specifically be carbon that can absorb significant amounts of VOCsthrough high surface area such as activated carbon or activated charcoal(in some cases one gram of activated carbon has a surface area in excessof 3,000 m² or more) and/or through the use of chemical treatments toenhance absorption properties.

The breath sampling mask 200 can include various ports or conduits inand out of the breath sampling mask 200, some of which may be in fluidcommunication with valves or other components or portions of the breathsampling mask 200. By way of example, the breath sampling mask 200 caninclude one or more conduits 206, which can serve as a passageway forbreath samples, exhaust air, wires, or the like.

In the embodiment of FIG. 2, air is primarily drawn in through the maskhousing material itself, however, in other embodiments an incoming portor conduit can be used through which air is drawn in. FIG. 3 is aschematic view of a breath sampling mask 200 as worn by a patient 100 inaccordance with various embodiments herein. The breath sampling mask 200can include one or more elastic members 202, 204 configured to securethe breath sampling mask 200 to the patient's face. The breath samplingmask 200 can include various ports or conduits in and out of the breathsampling mask 200, some of which may be in fluid communication withvalves or other components or portions of the breath sampling mask 200.By way of example, in some embodiments, the breath sampling mask 200 caninclude an air intake port 308. When the patient creates a negativepressure inside the breath sampling mask 200, air can be drawn from theambient environment into the breath sampling mask 200 through the airintake port 308, as indicated in FIG. 3 by air inflow arrows 210, 212,214, and 216. The breath sampling mask 200 can also include one or moreconduits 206, which can serve as a passageway for breath samples,exhaust air, wires, or the like.

It may be desirable to pre-condition and/or filter the inhaled air priorto its passage through the mask housing or port 308. In someembodiments, a preconditioning unit (not shown) can be connected to anair intake port 308 via a suitable connector, such as a bayonetconnector. Pre-conditioning and/or filtering the inhaled air caninclude, but not be limited to, providing humidity control, providingtemperature control, filtering particulate matter from the air,filtering organic or inorganic matter, including VOCs, by providing foradsorption and/or absorption of compounds and/or particulates from theambient environment.

Referring now to FIG. 4, a schematic cutaway view of a breath samplingmask 200 as worn by a patient 100 is shown in accordance with variousembodiments herein. The breath sampling mask 200 includes a mask housing402 that is configured to cover a portion of the face of the patient100. The mask housing 402 can define an interior chamber 406, which canbe a breath receiving chamber. The breath sampling mask 200 can alsoinclude a nose clip member 404 connected to the mask housing 402 forhelping to secure the breath sampling mask 200 to the patient 100. Insome embodiments, the nose clip member 404 can work in collaborationwith the elastic members 202, 204, to form an air tight connection ofthe breath sampling mask 200 against the patient's face. In someembodiments, breath sampling mask 200 can include a gas outflow conduit206 in fluid communication with the breath receiving chamber.

The nose clip member 404 can take on various forms and be make ofvarious materials. In some embodiments, the nose clip member 404 caninclude a U-shaped or V-shaped member which can exert at least somepressure on a patient's nose from two-directions that are at leastpartially opposed. In some embodiments, the nose clip member 404 caninclude a spring-like element which can expand under applied force toallow the nose clip member to fit over a patient's nose, but then exertpressure on the nose when the applied force is released. Materials usedto form the nose clip member 404 can include, but are not limited to,polymers, metals, composites, and the like.

In various embodiments, the breath sampling mask 200 can include aone-way airflow valve 408. The one-way airflow valve 408 can be in fluidcommunication between the air intake port 308 and the interior chamber406, the one-way airflow valve 408 only allowing a flow of air from thearea outside of the mask housing 402 into the interior chamber 406. Insome embodiments, a filter can be placed in fluid communication withone-way airflow valve 408 such that it can remove particulate orchemical impurities from the environmental air prior to being inhaled bypatient 100. In some embodiments, the filter can be integrated with thevalve 408 structure. The filter can do one or more of filter outparticulate matter from inspired air, provide humidity control, providea filter for organic or inorganic matter, and/or provide for adsorptionof compounds and/or particulates in the ambient environment. By way ofexample, the filter can include a carbon material, such as thosedescribed above, to filter out environmental particulates and/orenvironmental volatile organic compounds (VOCs).

In some embodiments, the breath sampling mask 200 can include a sensor410 that can be connected to the nose clip member 404. In someembodiments, the sensor 410 can be configured to contact the skin of thepatient 100 when the mask housing 402 is worn by the patient 100. Thesensor 410 can be selected from a group including a temperature sensor,a heart rate sensor, and a blood pressure sensor.

It will be appreciated that while the sensor 410 in FIG. 4 is shown asbeing connected to the nose clip member 404 and in contact with the skinof the patient, other embodiments for the sensor 410 can becontemplated. For example, in some embodiments the sensor 410 caninclude an ear clip sensor, a fingertip sensor, a carotid artery sensor,or a galvanic skin sensor that is not integral with the mask, butconnected to the mask housing via a wired or wireless connection. Insome embodiments the sensor 410 can include non-contact sensors (e.g.,that does not contact the skin), such as those used inelectromagnetic-based, laser-based, and image-based sensor systems.

In some embodiments, the breath sampling mask 200 can also includeadditional sensors 412, 414, which can be on the outside of the breathsampling mask 200 or on the inside of the breath sampling mask 200.Exemplary sensors can include an ambient temperature sensor, an ambienthumidity sensor, an internal temperature sensor, and an internalhumidity sensor.

While the embodiment of FIG. 4 shows a single chamber inside the mask,it will be appreciated that other embodiments of masks herein caninclude multiple chambers that are isolated from one another. The maskcan be configured to allow air and breath samples to move through thechambers of the mask in only a particular way or direction. FIG. 5 is aschematic cutaway view of a breath sampling mask 200 as worn by apatient in accordance with various embodiments herein. In thisembodiment, the breath receiving chamber includes dividing wall 506 toisolate breath receiving chamber into a nasal chamber 502 and a mouthchamber 504, as defined by the mask housing 402. The nasal chamber 502and the mouth chamber 504 can be separated from one another when thebreath sampling mask 200 comes into contact with the face of patientduring usage.

Separating the interior volume defined by the mask housing 402 intonasal chambers 502 and mouth chambers 504, in combination with valves,can allow for a controlled unidirectional flow of air through the breathsampling mask 200. In particular, the one-way airflow valve 408 onlyallows a flow of air from the area outside of the mask housing 402 intothe nasal chamber 502 through air intake port 308. Further anotherone-way airflow valve 508 only allows a flow of air from the mouthchamber 504 out through conduit 206. In this manner, air only movesthrough the chambers of the breath sampling mask 200 in one direction.It will be appreciated that while air intake port 308 and one-wayairflow valve 408 are shown disposed in the mask housing 402 within thenasal chamber 502, the air intake port 308 and one-way airflow valve 408can alternatively be disposed in the mask housing 402 within the mouthchamber 504. In some embodiments, the air intake port 308 and one-wayairflow valve 408 can be disposed in the mask housing 402 in both thenasal chamber 502 and within the mouth chamber 504. In some embodiments,breath sampling mask 200 can include a gas outflow conduit 206 in fluidcommunication with the nasal chamber 502, the mouth chamber 504, orboth.

In some embodiments, it may be desirable to retain a breath samplewithin the breath sampling mask 200 itself or another associatedstructure. For example, a container can be used to hold a breath sample,and the container itself can be disposed in the breath sampling mask 200or otherwise in fluid communication with the breath sampling mask 200.Referring now to FIG. 6, a schematic cutaway view of a breath samplingmask 200 as worn by a patient 100 is shown in accordance with variousembodiments herein. In this view, a breath sample container 602 isdisposed within the mouth chamber 504. The breath sample container 602can define an interior volume 604 in order to hold and retain a breathsample. It will be appreciated that while the breath sample container602 shown in FIG. 6 is removable, in another embodiment, breath samplecontainer 602 could be an integral part of the breath sampling mask 200.

Breath sampling masks in accordance with embodiments herein can formparts of breath sampling systems. Such breath sampling systems caninclude a breath sampling mask along with other components such aschemical sensors including sensing elements and circuitry for generatingsignals based on electrical properties of the sensing elements.Referring now to FIG. 7, a schematic view is shown of a breath samplingsystem 700 in accordance with various embodiments herein. The breathsampling system 700 can include breath sampling mask 200, which can beworn by a patient 100. In the embodiment shown in FIG. 7, air can beinspired into a nasal chamber 502 and into the lungs of the patient 100.This air can then be expired out into a mouth chamber 504 before passingout through conduit 206 and on to a gaseous analyte sensing device 702for analysis.

The gaseous analyte sensing device 702 can include a housing 718. Thegaseous analyte sensing device 702 can be connected to breath samplingmask 200 via conduit 206, through which a patient's gaseous breathsample can travel to be evaluated at gaseous analyte sensing device 702.The patient's gaseous breath sample can pass through an evaluationsample (patient sample) input port 704. The gaseous analyte sensingdevice 702 can also include a control sample (environment) input port706. The gaseous analyte sensing device 702 can also include a chemicalsensor element chamber 708, into which a chemical sensor element can beplaced. The gaseous analyte sensing device 702 can also include adisplay screen 710 and a user input device 712, such as a keyboard. Thegaseous analyte sensing device 702 can also include a gas outflow port714. The gaseous analyte sensing device 702 can also include flowsensors in fluid communication with the gas flow associated with one ormore of the evaluation sample input port 704 and control sample inputport 706. It will be appreciated that many different types of flowsensors can be used. In some embodiments, a hot-wire anemometer can beused to measure the flow of air. In some embodiments, the gaseousanalyte sensing device 702 can include a CO₂ sensor in fluidcommunication with the gas flow associated with one or more of theevaluation sample input port 704 and control sample input port 706.

In various embodiments, the gaseous analyte sensing device 702 can alsoinclude other functional components. By way of example, the gaseousanalyte sensing device 702 can include a humidity control module 716and/or a temperature control module 720. The humidity control module 716can be in fluid communication with the gas flow associated with one ormore of the evaluation sample input port 704 and control sample inputport 706 in order to adjust the humidity of one or both gas flow streamsin order to make the relative humidity of the two streams substantiallythe same in order to prevent an adverse impact on the readings obtainedby the system. The temperature control module 720 can be in fluidcommunication with the gas flow associated with one or more of theevaluation sample input port 704 and control sample input port 706 inorder to adjust the temperature of one or both gas flow streams in orderto make the temperature of the two streams substantially the same inorder to prevent an adverse impact on the readings obtained by thesystem. By way of example, the air flowing into the control sample inputport can be brought up to 37 degrees Celsius in order to match thetemperature of air coming from a patient. The humidity control moduleand the temperature control module can be upstream from the input ports,within the input ports, or downstream from the input ports in thehousing 718 of the gaseous analyte sensing device 702. In someembodiments, the humidity control module 716 and the temperature controlmodule 720 can be integrated.

In some embodiments, breath samples can be put into contact with achemical sensor element in the mask itself or in a structure directlyattached to the mask. One or more components of the gaseous analytesensing device 702 shown in reference to FIG. 7 can be integrated intothe breath sampling mask 200. As such, in some embodiments, a separategaseous analyte sensing device may not be needed in a breath sensingsystem. Referring now to FIG. 8, a schematic view is shown of a breathsampling system 800 in accordance with various embodiments herein. Thebreath sampling system 800 can include a breath sampling mask 200including a nasal chamber 502 and a mouth chamber 504. A chemical sensorholder 802 can be disposed within a breath receiving chamber, such asmouth chamber 504. The chemical sensor holder 802 can be configured toallow removable mounting of a chemical sensor element. The chemicalsensor element can interface with a breath sample collected through thebreath sampling mask 200 when the patient 100 exhales into the breathsampling mask 200. Exemplary chemical sensor elements will be describedmore fully below in reference to FIGS. 18-21.

Sample gas (breath) can optionally pass through a structure 806 such asa filter or valve and into the chemical sensor holder 802. Afterentering the chemical sensor holder 802, the gas can then pass out ofthe system through an exhaust port 804. Measurement circuitry (not shownin this view) can be associated with the chemical sensor holder 802 inorder to generate a signal based on an electrical property of thechemical sensor element. The signal(s) can be conveyed to an analysisdevice 810 through a data conduit 808. It will be appreciated, however,that signals can also be conveyed wirelessly. Referring now to FIG. 9, aschematic view is shown of a breath sampling system 900 in accordancewith various embodiments herein. In this embodiment, the breath samplingsystem 900 includes communication circuitry and an antenna 902 in orderto generate wireless signals that can be received by an analysis device810.

In some embodiments, the chemical sensor holder 802 can be housed in aseparate structure that can be attached (removably or not) to the breathsampling mask 200. Referring now to FIG. 10, a schematic view is shownof a breath sampling system 1000 in accordance with various embodimentsherein. In this embodiment, a chemical sensor holder housing 1002 isincluded. The chemical sensor holder housing can be in fluidcommunication with the breath receiving chamber. Sample gas can passfrom the mouth chamber 504 into chemical sensor holder housing 1002 and,specifically, into the chemical sensor holder 802 located within thechemical sensor holder housing 1002. Sample gas can pass over chemicalsensor element (not shown), secured by chemical sensor holder 802, andout exhaust port 804.

It will be appreciated that mask herein can take on many differentspecific forms. Referring now to FIG. 11, a schematic view is shown of abreath sampling system 1100 in accordance with various embodimentsherein. The breath sampling system 1100 can include breath sampling mask200, which can be worn by a patient 100. Breath sampling mask 200 caninclude nose clip member 404 for helping to secure the breath samplingmask 200 to the patient 100. In the embodiment shown in FIG. 11, air canbe inspired into the mask and into the lungs of the patient 100. Thisair can then be expired out into a mouth chamber before passing outthrough conduit 206 and on to a gaseous analyte sensing device 702. Insome embodiments, the breath sampling mask 200 and gaseous analytesensing device 702 can be connected directly via a data conduit, such asdata conduit 808 shown in FIG. 8. In other embodiments, the breathsampling mask 200 and gaseous analyte sensing device 702 can beconnected wirelessly.

The embodiment of breath sampling mask 200 shown in FIG. 11 will bedescribed in more detail in reference to FIGS. 12-17. Referring now toFIG. 12, a schematic side view of an exterior of breath sampling mask200 is shown. Breath sampling mask 200 can include air intake port 308that can be in fluid communication with a one-way airflow valve on theinterior (not shown) of the breath sampling mask 200. The breathsampling mask 200 can include one or more elastic members 202 and 204configured to secure the breath sampling mask 200 to the patient's face.The breath sampling mask 200 can include various ports or conduits inand out of the breath sampling mask 200, some of which may be in fluidcommunication with valves, filters, or other components or portions ofthe breath sampling mask 200. By way of example, the breath samplingmask 200 can include one or more conduits 206, which can serve as apassageway for breath samples, exhaust air, wires, or the like. Likestructures of breath sampling mask 200 are shown in a schematicisometric view in FIG. 13 and in a schematic top plan view in FIG. 14.

Referring now to FIG. 15, a schematic cross-sectional view of a side ofthe breath sampling mask 200 is shown. Breath sampling mask 200 caninclude nose clip member 404 attached to mask housing 402. In someembodiments, one or more sensors 410 can be connected to the nose clipmember 404, the one or more sensors 410 configured to contact the skinof the patient 100 when the breath sampling mask 200 is worn by thepatient 100. The sensor 410 can be selected from a group including atemperature sensor, a heart rate sensor, and a blood pressure sensor.

Breath sampling mask 200 can also include a nasal chamber 502 and amouth chamber 504. Nasal chamber 502 and mouth chamber 504 can beseparated by a dividing wall 506. It will be appreciated that in someembodiments the nasal chamber 502 defines the breath receiving chamber,while in other embodiments the mouth chamber can define the breathreceiving chamber. In some embodiments, both the nasal chamber 502 andthe mouth chamber can define the breath receiving chamber. In someembodiments, breath sampling mask 200 does not have a dividing wall 506.Mouth chamber 504 can include a dividing member 1502 that can span atleast a portion of mouth chamber 504 without completely dividing mouthchamber 504 into more than one section. Attached to dividing member 1502can be a chemical sensor holder 802. Chemical sensor holder 802 canserve as an anchor point to secure a chemical sensor element (not shown)within the interior, or patient-facing side, of breath sampling mask200.

Like structures of breath sampling mask 200 are shown in a schematicisometric view in FIG. 16 and in a schematic bottom plan view in FIG.17. FIG. 17 further shows that breath sampling mask 200 can include aone-way airflow valve 408 that can be in fluid communication with aone-way airflow valve on the exterior (not shown) of the breath samplingmask 200.

Referring now to FIG. 18, a schematic top plan view of a chemical sensorelement 1800 is shown in accordance with various embodiments herein. Thechemical sensor element 1800 can include a substrate 1802. It will beappreciated that the substrate can be formed from many differentmaterials. By way of example, the substrate can be formed from polymers,metals, glasses, ceramics, cellulosic materials, composites, metaloxides, and the like. The thickness of the substrate can vary. In someembodiments, the substrate has sufficient structural integrity to behandled without undue flexure that could damage components thereon. Insome embodiments, the substrate can have a thickness of about 0.05 mm toabout 5 mm. The length and width of the substrate can also vary. In someembodiments, the length (or major axis) can be from about 0.2 cm toabout 10 cm. In some embodiments, the width (perpendicular to the majoraxis) can be from about 0.2 cm to about 8 cm. In some embodiments, thechemical sensor element can be disposable. In some embodiments, thechemical sensor element can be reusable.

The chemical sensor element can include a first measurement zone 1804disposed on the substrate 1802. In some embodiments, the firstmeasurement zone 1804 can define a portion of a first gas flow path. Thefirst measurement zone (or breath sample zone) 1804 can include aplurality of discrete binding detectors that can sense analytes in agaseous sample, such as a breath sample. A second measurement zone (orenvironment sample zone) 1806, separate from the first measurement zone1804, can also be disposed on the substrate 1802. The second measurementzone 1806 can also include a plurality of discrete binding detectors. Insome embodiments, the second measurement zone 1806 can include the same(in type and/or number) discrete binding detectors that are within thefirst measurement zone 1804. In some embodiments, the second measurementzone 1806 can include only a subset of the discrete binding detectorsthat are within the first measurement zone 1804. In operation, the datagathered from the first measurement zone, which can be reflective of thegaseous sample analyzed, can be corrected or normalized based on thedata gathered from the second measurement zone, which can be reflectiveof analytes present in the environment. However, in some embodiments,both a first and second measurement zone can reflect the breath sampleanalyzed. In some embodiments, a second measurement zone is notincluded.

In some embodiments, a third measurement zone (drift control or witnesszone) 1808 can also be disposed on the substrate. The third measurementzone 1808 can include a plurality of discrete binding detectors. In someembodiments, the third measurement zone 1808 can include the same (intype and/or number) discrete binding detectors that are within the firstmeasurement zone 1804. In some embodiments, the third measurement zone1808 can include only a subset of the discrete binding detectors thatare within the first measurement zone 1804. In some embodiments, thethird measurement zone 1808 can include discrete binding detectors thatare different than those of the first measurement zone 1804 and thesecond measurement zone 1806. In some embodiments, a third measurementzone 1808 is not included. Aspects of the third measurement zone aredescribed in greater detail below.

The first measurement zone, the second measurement zone, and the thirdmeasurement zone can be the same size or can be of different sizes. Insome embodiments, the chemical sensor element 1800 can also include acomponent 1810 to store reference data. The component 1810 to storereference data can be an electronic data storage device, an optical datastorage device, a printed data storage device (such as a printed code),or the like. The reference data can include, but is not limited to, dataregarding the third measurement zone.

In some embodiments, chemical sensor elements embodied herein caninclude electrical contacts (not shown) that can be used to providepower to components on the chemical sensor element 1800 and/or can beused to read data regarding the measurement zones and/or data from thestored in component 1810. However, in other embodiments there are noexternal electrical contacts on the chemical sensor element 1800.

Chemical sensor element 1800 can be configured to fit within chemicalsensor holder 802, shown in FIGS. 8-10 and 15-17. Further aspects ofexemplary chemical sensor elements can be found in U.S. application Ser.No. 14/883,895, the content of which is herein incorporated by referencein its entirety.

Many different types of circuits can be used to gather data fromchemical sensor elements. It will be appreciated that the chemicalsensor elements embodied herein can include those that are compatiblewith passive wireless sensing techniques. One example of a passivesensor circuit 2202 and a portion of a reading circuit 2222 isillustrated schematically in FIG. 22 and discussed in more detail below,however, many other circuits are contemplated herein.

Referring now to FIG. 19, a schematic diagram of a portion of ameasurement zone 1900 is shown in accordance with various embodimentsherein. A plurality of discrete binding detectors 1902 can be disposedwithin the measurement zone 1900 in an array. In some embodiments, achemical sensor element can include a plurality of discrete bindingdetectors configured in an array within a measurement zone. In someembodiments, the plurality of discrete binding detectors can beidentical, while in other embodiments the plurality of discrete bindingdetectors can be different from one another.

In some embodiments, the discrete binding detectors can be heterogeneousin that they are all different from one another in terms of theirbinding behavior or specificity with regard a particular analyte. Insome embodiments, some discrete binding detectors can be duplicated forvalidation purposes, but are otherwise heterogeneous from other discretebinding detectors. Yet in other embodiments, the discrete bindingdetectors can be homogeneous. While the discrete binding detectors 1902of FIG. 19 are shown as boxes organized into a grid, it will beappreciated that the discrete binding detectors can take on manydifferent shapes (including, but not limited to, various polygons,circles, ovals, irregular shapes, and the like) and, in turn, the groupsof discrete binding detectors can be arranged into many differentpatterns (including, but not limited to, star patterns, zig-zagpatterns, radial patterns, symbolic patterns, and the like).

In some embodiments, the order of specific discrete binding detectors1902 across the length 1912 and width 1914 of the measurement zone canbe substantially random. In other embodiments, the order can bespecific. For example, in some embodiments, a measurement zone can beordered so that the specific discrete binding detectors 1902 foranalytes having a lower molecular weight are located farther away fromthe incoming gas flow relative to specific discrete binding detectors1902 for analytes having a higher molecular weight which are locatedcloser to the incoming gas flow. As such, chromatographic effects whichmay serve to provide separation between chemical compounds of differentmolecular weight can be taken advantage of to provide for optimalbinding of chemical compounds to corresponding discrete bindingdetectors.

The number of discrete binding detectors within a particular measurementzone can be from about 1 to about 100,000. In some embodiments, thenumber of discrete binding detectors can be from about 1 to about10,000. In some embodiments, the number of discrete binding detectorscan be from about 1 to about 1,000. In some embodiments, the number ofdiscrete binding detectors can be from about 2 to about 500. In someembodiments, the number of discrete binding detectors can be from about10 to about 500. In some embodiments, the number of discrete bindingdetectors can be from about 50 to about 500. In some embodiments, thenumber of discrete binding detectors can be from about 1 to about 250.In some embodiments, the number of discrete binding detectors can befrom about 1 to about 50.

Each of the discrete binding detectors suitable for use herein caninclude at least a portion of one or more electrical circuits. By way ofexample, in some embodiments, each of the discrete binding detectors caninclude one or more passive electrical circuits. In some embodiments,the graphene varactors can be included such that they are integrateddirectly on an electronic circuit. In some embodiments, the graphenevaractors can be included such that they are wafer bonded to thecircuit. In some embodiments, the graphene varactors can includeintegrated readout electronics, such as a readout integrated circuit(ROIC). The electrical properties of the electrical circuit, includingresistance or capacitance, can change upon binding, such as specificand/or non-specific binding, with a component from a breath sample.

In some embodiments, the discrete binding detectors embodied herein caninclude graphene-based variable capacitors (or graphene varactors).Referring now to FIG. 20, a schematic view of a graphene varactor 2000is shown in accordance with the embodiments herein. It will beappreciated that graphene varactors can be prepared in various ways withvarious geometries, and that the graphene varactor shown in FIG. 20 isjust one example in accordance with the embodiments herein.

Graphene varactor 2000 can include an insulator layer 2002, a gateelectrode 2004 (or “gate contact”), a dielectric layer (not shown inFIG. 20), one or more graphene layers, such as graphene layers 2008 aand 2008 b, and a contact electrode 2010 (or “graphene contact”). Insome embodiments, the graphene layer(s) 2008 a-b can be contiguous,while in other embodiments the graphene layer(s) 2008 a-b can benon-contiguous. Gate electrode 2004 can be deposited within one or moredepressions formed in insulator layer 2002. Insulator layer 2002 can beformed from an insulative material such as silicon dioxide, formed on asilicon substrate (wafer), and the like. Gate electrode 2004 can beformed by an electrically conductive material such as chromium, copper,gold, silver, tungsten, aluminum, titanium, palladium, platinum,iridium, and any combinations or alloys thereof, which can be depositedon top of or embedded within the insulator layer 2002. The dielectriclayer can be disposed on a surface of the insulator layer 2002 and thegate electrode 2004. The graphene layer(s) 2008 a-b can be disposed onthe dielectric layer. The dielectric layer will be discussed in moredetail below in reference to FIG. 21.

Graphene varactor 2000 includes eight gate electrode fingers 2006 a-2006h. It will be appreciated that while graphene varactor 2000 shows eightgate electrode fingers 2006 a-2006 h, any number of gate electrodefinger configurations can be contemplated. In some embodiments, anindividual graphene varactor can include fewer than eight gate electrodefingers. In some embodiments, an individual graphene varactor caninclude more than eight gate electrode fingers. In other embodiments, anindividual graphene varactor can include two gate electrode fingers. Insome embodiments, an individual graphene varactor can include 1, 2, 3,4, 5, 6, 7, 8, 9, 10, or more gate electrode fingers. Graphene varactor2000 can include one or more contact electrodes 2010 disposed onportions of the graphene layers 2008 a and 2008 b. Contact electrode2010 can be formed from an electrically conductive material such aschromium, copper, gold, silver, tungsten, aluminum, titanium, palladium,platinum, iridium, and any combinations or alloys thereof. Furtheraspects of exemplary graphene varactors can be found in U.S. Pat. No.9,513,244, the content of which is herein incorporated by reference inits entirety.

Referring now to FIG. 21, a schematic cross-sectional view of a portionof a graphene varactor 2100 is shown in accordance with variousembodiments herein. The graphene varactor 2100 can include an insulatorlayer 2002 and a gate electrode 2004 recessed into the insulator layer2002. The gate electrode 2004 can be formed by depositing anelectrically conductive material in the depression in the insulatorlayer 2002, as discussed above in reference to FIG. 20. A dielectriclayer 2102 can be formed on a surface of the insulator layer 2002 andthe gate electrode 2004. In some examples, the dielectric layer 2102 canbe formed of a material, such as, silicon dioxide, aluminum oxide,hafnium dioxide, zirconium dioxide, hafnium silicate, or zirconiumsilicate.

The graphene varactor 2100 can include a single graphene layer 2104 thatcan be disposed on a surface of the dielectric layer 2102. The graphenelayer 2104 can be surface-modified with a modification layer 2106. Itwill be appreciated that in some embodiments, the graphene layer 2104 isnot surface-modified.

The breath sensing systems described herein can include circuitry forgenerating signals from the discrete binding detectors. Such circuitrycan include active and passive sensing circuits. Such circuitry canimplement wired (direct electrical contact) or wireless sensingtechniques. Referring now to FIG. 22, a schematic diagram of a passivesensor circuit 2202 and a portion of a reading circuit 2222 is shown inaccordance with various aspects herein. In some embodiments, the passivesensor circuit 2202 can include a metal-oxide-graphene varactor 2204(wherein RS represents the series resistance and CG represents thevaractor capacitor) coupled to an inductor 2210. In some embodiments,the reading circuit 2222 can include a reading coil having a resistance2224 and an inductance 2226. However, it will be appreciated that thecircuits shown in FIG. 22 are merely one approach. Many differentapproaches are contemplated herein.

In some embodiments, a method of determining the presence of one or moredisease states in a patient is included. The method can include puttinga breath sampling mask on a patient and alerting the patient to breathein and out to generate a breath sample. The method can includecontacting the breath sample with a chemical sensor element. The methodcan further include collecting data from chemical sensor elementcomprising a plurality of discrete binding detectors. The method canfurther include using a measurement circuit to generate signals from thediscrete binding detectors. The method can further include evaluatingthe signals by comparing them to previously obtained sets of signals orsignal patterns.

In some embodiments, the method can include alerting the patient tobreathe in through the nose and out through the mouth to generate abreath sample. In some embodiments, the method can include instructingthe patient to breathe in through the mouth and out through the mouth.In some embodiments, the method can include instructing the patient tobreathe in through the mouth and out through the nose. In yet otherembodiments, the method can include instructing the patient to breathein through the nose and out through the nose.

In some embodiments, the method can include evaluating the signals bycomparing them to previously obtained sets of signals or patterns forpatients in a non-diseased or diseased state. In some embodiments, thediseased state can include, but not be limited to cancer, including lungcancer, blood-borne cancers, prostate cancer, rectal cancer, breastcancer, liver cancer, pancreatic cancer, chronic obstructive pulmonarydisease, diabetes, heart failure, and the like. In some embodiments, thecomparison can include detecting patterns of differentiation betweennon-diseased and diseased states. In some embodiments, the method caninclude detecting one or more volatile organic compounds in the breathof a patient.

It should be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to a composition containing “a compound” includes a mixture oftwo or more compounds. It should also be noted that the term “or” isgenerally employed in its sense including “and/or” unless the contentclearly dictates otherwise.

It should also be noted that, as used in this specification and theappended claims, the phrase “configured” describes a system, apparatus,or other structure that is constructed or configured to perform aparticular task or adopt a particular configuration to. The phrase“configured” can be used interchangeably with other similar phrases suchas arranged and configured, constructed and arranged, constructed,manufactured and arranged, and the like.

All publications and patent applications in this specification areindicative of the level of ordinary skill in the art to which thistechnology pertains. All publications and patent applications are hereinincorporated by reference to the same extent as if each individualpublication or patent application was specifically and individuallyindicated by reference. The publications and patents disclosed hereinare provided solely for their disclosure. Nothing herein is to beconstrued as an admission that the inventors are not entitled toantedate any publication and/or patent, including any publication and/orpatent cited herein.

The technology has been described with reference to various specific andpreferred embodiments and techniques. However, it should be understoodthat many variations and modifications may be made while remainingwithin the spirit and scope of the technology. As such, the embodimentsof the present technology described herein are not intended to beexhaustive or to limit the technology to the precise forms disclosed inthe following detailed description. Rather, the embodiments are chosenand described so that others skilled in the art can appreciate andunderstand the principles and practices of the present technology.

1. A breath sensing system comprising: a breath sampling mask comprisinga mask housing configured to cover a portion of the face of a patient,the mask housing defining a breath receiving chamber; and a volatileorganic compound filter; a chemical sensor element for sensing volatileorganic compounds in fluid communication with the breath sampling mask,the chemical sensor element comprising a plurality of discrete bindingdetectors, wherein the chemical sensor element interfaces with a breathsample collected through the breath sampling mask.
 2. The breath sensingsystem of claim 1, further comprising circuitry for generating signalsfrom the discrete binding detectors.
 3. The breath sensing system ofclaim 1, a breath sampling mask further comprising a nose clip forhelping to secure the breath sampling mask to the face of a patient. 4.The breath sensing system of claim 1, further comprising a sensorcomprising one or more of a temperature sensor, a heart rate sensor, anda blood pressure sensor.
 5. The breath sensing system of claim 1,further comprising a sensor comprising one or more of an ambienttemperature sensor, an ambient humidity sensor, an internal temperaturesensor, and an internal humidity sensor.
 6. The breath sensing system ofclaim 1, further comprising a removable breath sample container disposedwithin the mouth chamber.
 7. The breath sensing system of claim 1,further comprising a gas outflow conduit in fluid communication with thebreath receiving chamber.
 8. The breath sensing system of claim 1,further comprising a chemical sensor holder configured to allowremovable mounting of a chemical sensor element.
 9. The breath sensingsystem of claim 8, wherein the chemical sensor holder is disposed withinthe breath receiving chamber.
 10. The breath sensing system of claim 1,further comprising a chemical sensor holder housing in fluidcommunication with the breath receiving chamber; wherein the chemicalsensor element is disposed within the chemical sensor holder housing.11. The breath sensing system of claim 1, further comprising a filter influid communication with the one-way airflow valve.
 12. A breathsampling mask comprising: a mask housing configured to cover a portionof the face of a patient, the mask housing defining a chamber; the maskconfigured to remove volatile organic compounds from air drawn inthrough the mask housing.
 13. The breath sampling mask of claim 12,further comprising a sensor comprising one or more of a temperaturesensor, a heart rate sensor, and a blood pressure sensor.
 14. The breathsampling mask of claim 12, further comprising a nose clip member forhelping to secure the breath sampling mask to the patient.
 15. Thebreath sampling mask of claim 14, further comprising a sensor attachedto the nose clip member.
 16. The breath sampling mask of claim 12, themask housing further comprising a dividing wall isolating the chamberinto a nasal chamber and a mouth chamber.
 17. The breath sampling maskof claim 16, further comprising a one-way airflow valve in fluidcommunication with the nasal chamber and an area outside of the maskhousing, the one-way airflow valve only allowing a flow of air from thearea outside of the mask housing into the nasal chamber.
 18. The breathsampling mask of claim 16, further comprising a chemical sensor holderconfigured to allow removable mounting of a chemical sensor element,wherein the chemical sensor holder is disposed within the mouth chamber.19. The breath sampling mask of claim 12, further comprising a sensorcomprising one or more of an ambient temperature sensor, an ambienthumidity sensor, an internal temperature sensor, and an internalhumidity sensor.
 20. A method of determining the presence of one or moredisease states of a patient comprising: putting a breath sampling maskon a patient; alerting the patient to breathe in and out to generate abreath sample; contacting the breath sample with a chemical sensorelement, the chemical sensor element comprising a plurality of discretebinding detectors; using a measurement circuit to generate signals fromthe discrete binding detectors; and evaluating the signals by comparingthem to previously obtained sets of signals or signal patterns.